Hephaestin-like protein 1 (HEPHL1)

Hephaestin-like protein 1 (HEPHL1), also called zyklopen, is a copper-dependent multicopper ferroxidase enzyme located on cellular membranes, involved in the oxidation of Fe²⁺ (ferrous) to Fe³⁺ (ferric), thereby supporting iron export and homeostasis in specific tissues[1][2][3]. Structurally, HEPHL1 resembles its homologs ceruloplasmin and hephaestin, with six copper-binding domains crucial for its function[2]. Functional HEPHL1 is vital for maintaining normal intracellular iron levels, supporting iron-dependent processes, and regulating the activity of other copper-dependent enzymes such as lysyl oxidase, which is important for connective tissue and hair formation. Loss-of-function mutations are implicated in disorders such as abnormal hair development, cognitive dysfunction, and increased intracellular iron[2][3]. HEPHL1 also appears relevant in certain cancers and neurodevelopmental diseases, and is differentially expressed in tissues such as placenta, mammary gland, and embryonic structures, but not liver or serum, indicating tissue-specific functions. No clinically approved drugs directly target HEPHL1, and the protein has not currently been validated as a direct pharmacological target, though its role in disease development is under investigation[1][2].

Other names

hephaestin like 1zyklopenferroxidase HEPHL1DKFZp686F22190Zphephaestin-like protein 1HJDDZP